1. Field of the Invention
This invention relates to novel antibacterial agents which are of value as animal feed supplements, as therapeutic agents for the control of infectious diseases caused by gram-positive and gram-negative bacteria, and for the sterilization of hospital surfaces and the like; and to novel intermediates for their production. More specifically, the antibacterial compounds of the instant invention are 6-acyl derivatives of 6-amino-2,2-dimethylpenam, which also bear a 5-tetrazolyl group or certain 1- or 2-substituted 5-tetrazolyl groups at the 3-position of the penam nucleus.
2. Description of the Prior Art
In spite of the large number of penam derivatives which have been proposed for use as antibacterial agents, there still exists a need for new agents.
U.S. Pat. Nos. 3,427,302 and 3,468,874 disclose penam derivatives which incorporate a tetrazolyl group as part of the 6-acylamino substituent; however, the compounds of the instant invention are unique in having a tetrazolyl group bonded directly to the penam nucleus.
The vast majority of penam compounds disclosed in the prior art have a carboxylic acid group (or a salt thereof) attached to the 3-position. However, penam compounds with other carboxylic acid derivatives at the C-3 locus are also known. Penam-3-carboxylic acid esters have been disclosed, for example, by Kirchner et al., Journal of Organic Chemistry, 14, 388 (1949); Carpenter, Journal of the American Chemical Society, 70, 2964 (1948); Johnson, Journal of the American Chemical Society, 75, 3636 (1953); Barnden et al., Journal of the Chemical Society (London), 3733 (1953) and Jansen and Russell, Journal of the Chemical Society (London), 2127 (1965); and penam-3-carboxamides have been reported, for example, by Holysz and Stavely, Journal of the American Chemical Society, 72, 4760 (1950), Huang et al., Antimicrobial Agents and Chemotherapy, 493 (1963) and U.S. Pat. No. 3,641,000. Peron et al. (Journal of Medicinal Chemistry, 7, 483 [1964]) prepared several 6-(substituted amino)-2,2-dimethyl-penam-3-carboxylic acid azides, which were subsequently converted into the corresponding 3-isocyanates and 3-benzylcarbamates. Peron et al. (loc. cit.) also reported certain 3-(hydroxymethyl)penam derivatives. Dehydration of the simple amide of benzylpenicillin yields the corresponding nitrile (Khokhlov et al., Doklady Akad. Sci. Nauk S.S.S.R., 135, 875 [1960]).